Chemokine usually has three β-sheets in its structure, and has an α-helix at C terminal and 4 conserved cysteines at N-terminus. In accordance with the sequence containing the first two cysteines at N-terminus, chemokine is divided as four groups, CXC, CC, C and CX3C, and CC and CXC chemokines are the major ones. Reaction happens after chemokine on the cell conjugated with chemokine receptor. Chemokine receptor includes seven transmembrane G protein binding receptors, which respectively are nominated as CXCR, CCR, CXR and CX3CR according to the types of ligands on the binding target. Chemokine receptors are further arranged according to the number, such as CXCR1, CXCR2, CXCR4 and so on. However, not only one chemokine receptor is represented on the target cells, the binding target of the infiltrated inflammation cells is not specifically to one chemokine receptor, and then some chemokine receptors of different cells must be expressed under certain stimulation and induction.
For instance, ELR-CXC chemokine with glutamate (E)-leucine (L)-Arginine (R) characteristic sequence (ELR characteristic sequence) is referred to a protein having the amino acid sequence of ELR-CXC characteristic at N-terminus, and X would be the amino acid having polarity and w/o charge, or X is absent. ELR-CXC chemokine can regulate the expression of carcinogen, IL-8 and neutrophil-activating protein-2 (NAP-2). Its receptors are CXCR1 and CXCR2, and its major target cells are neutrophils, ELR-CXC chemokine can promote the accumulation and activation of neutrophils. Thus, this type of ELR-CXC chemokine plays an important role in the generation of the board-ranged acute and chronic inflammation diseases. These inflammations include psoriasis and rheumatoid arthritis.
Additionally, ELR-CXC chemokine further is associated with angiogenesis accompanied upon tumor development, and its inductive mechanism is the activation generated by conjugating this type of chemokine, especially referring to IL-8, with CXCR1 and CXCR2 on the endothelial cells (ECs). At present, it is proved that many different types of tumors are able to reproduce ELR-CXC chemokines, and the tumors expressing these types of chemokines are deemed to be associated with the tumor development after poor prognosis.
Anti-conjugation of CXCR1 or CXCR2 with ELR-CXC chemokine is a practicable strategy, so that the abnormal signal transmission induced by the activation of CXCR1 or/and CXCR2 receptor is inhibited, so that the associated diseases resulted from the activation of cells with two types of receptors are treated. Accordingly, scientists are endeavoring in finding and preparing receptor protein analogs for inhibiting CXC chemokines.
It is therefore attempted by the applicant to deal with the above situation encountered in the prior art.